The Role of Alcohol in Pancreatic Diseases: A Comprehensive Perspective.

Alcohol abuse is a leading cause of global health care concerns and can cause health loss, disease, and death. In addition to the liver, the pancreas is a vital organ for the metabolism of alcohol, especially nonoxidative metabolism, and alcohol abuse is the leading cause of pancreatic diseases worldwide. Epidemiologic investigations have shown that alcohol consumption is linked to a spectrum of multiple pancreatic disorders, including acute pancreatitis, chronic pancreatitis, pancreatic cancer, and diabetes. Numerous in vitro and in vivo studies have elucidated the key mechanisms related to alcohol-induced pancreatic tissue injury in recent years. Alcohol has hazardous effects on multiple organs, destroying pancreatic acinar, ductal, stellate, and β-cells. These mechanisms, mainly mediated by alcohol and alcohol metabolites, include oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, calcium overload, premature trypsinogen activation, inflammation, and extracellular matrix remodeling, which are complex and interrelated. A deeper understanding of these processes will open new avenues for therapeutic intervention. Although behavioral strategies, such as abstinence, remain essential, pharmacologic and molecularly targeted therapies offer potential complementary approaches. Given the challenges of maintaining sustained abstinence, these adjunctive treatments are critical for slowing or preventing the progression of alcohol-driven pancreatic diseases.